Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Pseudomyogenic hemangioendothelioma (PMHE), also referred to as epithelioid sarcoma–like hemangioendothelioma,¹ is a rare soft tissue tumor that was described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. It predominantly affects males between the second and fifth decades of life and most commonly presents as multiple nodules that may involve either the superficial or deep soft tissues of the legs and less often the arms. It also can arise on the trunk. We present a case of PMHE occurring in a young man and briefly review the literature on clinical presentation and histologic differentiation of this unique tumor, comparing these findings to its mimickers.

Case Report

A 20-year-old man presented with skin lesions on the left leg that had been present for 1 year. The patient described the lesions as tender pimples that would drain yellow discharge on occasion but had now transformed into large brown plaques. Physical examination showed 4 verrucous plaques ranging in size from 1 to 3 cm with hyperpigmentation and a central crust (Figure 1). Initially, the patient thought the lesions appeared due to shaving his legs for sports. He presented to the emergency department multiple times over the past year; pain control was provided and local skin care was recommended. Culture of the discharge had been performed 6 months prior to biopsy with negative results. No biopsy was performed on initial presentation and the lesions were diagnosed in the emergency department clinically as boils.

After failing to improve, the patient was seen by an outside dermatologist and the clinical differential diagnosis included deep fungal infection, atypical mycobacterial infection, and keloids. A 4-mm punch biopsy was taken from the periphery of one of the lesions and demonstrated hyperkeratosis, papillomatosis, and acanthosis (Figure 2). Within the superficial and deep dermis and focally extending into the subcutaneous tissue, there were sheets of spindled to epithelioid-appearing cells with moderate cytologic atypia (Figure 3). The tumor showed infiltrative margins. There was moderate cellularity. The individual cells had a rhabdoid appearance with large eccentric vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm (Figure 4). No definitive evidence of glandular, squamous, or vascular differentiation was present. There was an associated moderate inflammatory host response composed of neutrophils and lymphocytes. Occasional extravasated red blood cells were present. Immunohistochemistry staining was performed and the atypical cells demonstrated diffuse positive staining for friend leukemia integration 1 transcription factor (FLI-1), erythroblastosis virus E26 transforming sequence-related gene (ERG)(Figure 5), CD31, and CD68. There was patchy positive staining for cytokeratin AE1/AE3, CD10, and factor VIII. There was no remarkable staining for human herpesvirus 8, epithelial membrane antigen, S-100, CD34, cytokeratin 903, and desmin. Overall, the histologic features in conjunction with the immunohistochemistry staining were consistent with a diagnosis of PMHE.

Magnetic resonance imaging was then performed to evaluate the depth and extent of the lesions for surgical excision planning (Figure 6), which showed 5 nodular lesions within the dermis and subcutis adjacent to the proximal aspect of the left tibia and medial aspect of the left knee. An additional lesion was noted between the sartorius and semimembranosus muscles, which was thought to represent either a lymph node or an additional neoplastic lesion. Chest computed tomography also displayed indeterminate lesions in the lungs.

Excision of the superficial lesions was performed. All of the lesions demonstrated similar histologic changes to the previously described biopsy specimen. The tumor was limited to the dermis and subcutaneous tissue. The patient was lost to follow-up and the etiology of the lung lesions was unknown.

Comment

Nomenclature
Pseudomyogenic hemangioendothelioma is a relatively new type of vascular tumor that has been included in the updated 2013 edition of the World Health Organization classification as an intermediate malignant tumor that rarely metastasizes.³ It typically involves multiple tissue planes, most notably the dermis and subcutaneous layers but also muscle and bone.⁴ The term pseudomyogenic refers to the histologic resemblance of some of the cells to rhabdomyoblasts; however, these tumors are negative for all immunohistochemical muscle markers, most notably myogenin, desmin, and α-smooth muscle actin.⁵

Clinical Presentation
Gross features of PMHE typically include multiple firm nodules with ill-defined margins. The tumor was initially described in 1992 by Mirra et al² as a fibromalike variant of epithelioid sarcoma. In 2003, a series of 7 cases of PMHE was reported by Billings et al⁶ under the term epithelioid sarcomalike hemangioendothelioma. Other than the predominance of an epithelioid morphology, the cases reported as epithelioid sarcomalike hemangioendothelioma had similar clinical features and immunophenotype to what has been reported as PMHE.

Based on a PubMed search of articles indexed for MEDLINE using the term pseudomyogenic hemangioendothelioma, the 2 largest case series were reported by Pradhan et al⁷ (N=8) in 2017 and Hornick and Fletcher⁴ (N=50) in 2011. Hornick and Fletcher⁴ reported a male (41/50 [82.0%]) to female (9/50 [18.0%]) ratio of 4.6 to 1, and an average age at presentation of 31 years with 82% (41/50) of patients 40 years or younger. Pradhan et al⁷ also reported a male predominance (7/8 [87.5%]) with a similar average age at presentation of 29 years (age range, 9–62 years). The size of individual tumors ranged from 0.3 to 5.5 cm (mean size, 1.9 cm) in the series by Hornick and Fletcher⁴ and 0.3 to 6.0 com in the series by Pradhan et al.⁷ Hornick and Fletcher⁴ reported the most common site of involvement was the leg (27/50 [54.0%]), followed by the arm (12/50 [24.0%]), trunk (9/50 [18.0%]), and head and neck (2/50 [4.0%]). The leg (6/8 [75.0%]) also was the most common site of involvement in the series by Pradhan et al,⁷ with 2 cases occurring on the arm. In the series by Hornick and Fletcher,⁴ the tumors typically involved the dermis and subcutaneous tissue (26/50 [52%]) with a smaller number involving skeletal muscle (17/50 [34%]) and bone (7/50 [14%]). They reported 66% of their patients (33/50) had multifocal disease at presentation.⁴ Pradhan et al⁷ also reported 2 (25.0%) cases being limited to the superficial soft tissue, 2 (25.0%) being limited to the deep soft tissue, and 4 (50.0%) involving the bone; 5 (62.5%) patients had multifocal disease at presentation. The presentation of our patient in regards to gender, age, and tumor characteristics is consistent with other published cases.^5-10

Histopathology
Microscopic features of PMHE include sheets of spindled to epithelioid-appearing cells with mild to moderate nuclear atypia and eosinophilic cytoplasm. The tumor has an infiltrative growth pattern. Some of the cells may resemble rhabdomyoblastlike cells, hence the moniker pseudomyogenic. There is no recapitulation of vascular structures or remarkable cytoplasmic vacuolization. Mitotic rate is low and there is no tumor necrosis.⁴ The tumor cells do not appear to arise from a vessel or display an angiocentric growth pattern. Many cases report the presence of an inflammatory infiltrate containing neutrophils interspersed within the tumor.^4,5,7 The overlying epidermis will commonly show hyperkeratosis, epidermal hyperplasia, and acanthosis.^4,11

Differential Diagnosis
The histopathologic differential diagnosis would include epithelioid sarcoma, epithelioid hemangioendothelioma, and to a lesser extent dermatofibrosarcoma protuberans (DFSP) and rhabdomyosarcoma. Dermatofibrosarcoma protuberans is the most commonly encountered of these tumors. Histologically, DFSP is characterized by a cellular proliferation of small spindle cells with plump nuclei arranged in a storiform or cartwheel pattern. Dermatofibrosarcoma protuberans tends to be limited to the dermis and subcutaneous tissue and only rarely involves underlying skeletal muscle. The presence of the storiform growth pattern in conjunction with the lack of rhabdoid changes would favor a diagnosis of DFSP. Another characteristic histologic finding typically only associated with DFSP is the interdigitating growth pattern of the spindle cells within the lobules of the subcutaneous tissue, creating a lacelike or honeycomb appearance.

Immunohistochemistry staining is necessary to help differentiate PMHE from other tumors in the differential diagnosis. Pseudomyogenic hemangioendothelioma stains positive for cytokeratin AE1/AE3; integrase interactor 1; and vascular markers FLI-1, CD31, and ERG, and negative for CD34.^4,6,12-15 In contrast to epithelioid hemangioendothelioma, DFSP, and to a lesser extent epithelioid sarcoma, all of which are positive for CD34, epithelioid sarcoma is negative for both CD31 and integrase interactor 1. Dermatofibrosarcoma protuberans is negative for cytokeratin AE1/AE3. Rhabdomyosarcomas are positive for myogenic markers such as MyoD1 and myogenin, unlike any of the other tumors mentioned. Histologically, epithelioid sarcomas will tend to have a granulomalike growth pattern with central necrosis, unlike PMHE.¹² Epithelioid hemangioendothelioma often will have a cordlike growth pattern in a myxochondroid background. Unlike PMHE, these tumors often will appear to be arising from vessels, and intracytoplasmic vacuoles are common. Three cases of PMHE have been reported to have a t(7;19)(q22;q13) chromosomal anomaly, which is not consistent with every case.¹⁶

Treatment Options
Standard treatment typically includes wide excision of the lesions, as was done in our case. Because of the substantial risk of local recurrence, which was up to 58% in the series by Hornick and Fletcher,⁴ adjuvant therapy may be considered if positive margins are found on excision. Metastasis to lymph nodes and the lungs has been reported but is rare.^2,4 Most cases have been shown to have a favorable prognosis; however, local recurrence seems to be common. Rarely, amputation of the limb may be required.⁵ In contrast, epithelioid sarcomas have been found to spread to lymph nodes and the lungs in up to 50% of cases with a 5-year survival rate of 10% to 30%.¹³

Conclusion

In summary, we describe a case of PMHE involving the lower leg in a 20-year-old man. These tumors often are multinodular and multiplanar, with the dermis and subcutaneous tissues being the most common areas affected. It has a high rate of local recurrence but rarely has distant metastasis. Pseudomyogenic hemangioendothelioma, similar to other soft tissue tumors, can be difficult to diagnose on shave biopsy or superficial punch biopsy not extending into subcutaneous tissue. Deep incisional or punch biopsies are required to more definitively diagnose these types of tumors. The diagnosis of PMHE versus other soft tissue tumors requires correlation of histology and immunohistochemistry staining with clinical information and radiographic findings.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

Chemotherapy followed by radiation resulted in superior outcomes compared with concurrent chemoradiotherapy in patients with non–small-cell lung cancer (NSCLC) who had negative margins after surgery and pN2 disease, according to results of a retrospective analysis.

“We also found that sequential therapy is becoming the more frequent practice pattern over time for patients with R0 pN2 disease, and our results support this practice,” wrote Samual Francis, MD, of the University of Utah Huntsman Cancer Institute, Salt Lake City, and his coauthors.

By contrast, there was no clear association between treatment sequence and survival among patients who had positive margins after surgery in this analysis, authors of the study reported (J Clin Oncol. 2017 Dec 13. doi: 10.1200/JCO.2017.74.4771).

The study included 1,024 patients in National Cancer Database who received a diagnosis of nonmetastatic NSCLC and received chemotherapy and radiation concurrently or sequentially after surgery. Of those patients, 747 had R0 resections and pN2 nodal status, and the remainder had R1 or R2 resections and pN0-N2 disease.

For patients with R0 pN2 NSCLC, median overall survival was 58.8 months for sequential chemotherapy followed by radiation, versus 40.4 months for concurrent chemoradiotherapy (log-rank P less than .001), data show.

That association between sequential treatment and improved overall survival remained significant even after propensity score matching (hazard ratio [HR], 1.35; P = .019), investigators reported.

However, for the remaining cohort of patients with positive margins regardless of nodal status, there was no significant difference in overall survival favoring either approach (42.6 months for sequential versus 38.5 months for concurrent; log-rank P = .42), they added, and no clear association between treatment approaches (HR 1.35; P = .19).

The analysis covered patients diagnosed between 2006 and 2012, the most recent data period available.

Investigators were also able to identify changes in practice patterns over time using this data set. Between 2006 and 2012, there was an increase in the use of sequential chemotherapy and radiotherapy for patients with R0 resection and pN2 disease, and a decrease in the use of concurrent chemoradiotherapy.

Conversely, they found that for patients with positive margins, there was an increase over time in use of the concurrent approach and decrease in the sequential approach.

“These findings suggest practice patterns have shifted toward concordance with consensus guideline recommendations over time,” Dr. Francis and his colleagues said in their report.

Current guidelines advocate for chemotherapy followed by postoperative radiotherapy for patients with negative margins and pN2 disease, but suggest concurrent chemoradiotherapy for patients with positive margins, they added.

Dr. Francis had no relationships to disclose. Study coauthors reported disclosures related to Elekta, ProLung, Merit Medical Systems, and Bard Medical.

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at pdnews@frontlinemedcom.com.

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at pdnews@frontlinemedcom.com.

One thing that constantly surprises me about adolescent sleep is that neither the teen nor the parent is as concerned about it as I am. Instead, they complain about irritability, dropping grades, anxiety, depression, obesity, oppositionality, fatigue, and even substance use – all documented effects of sleep debt.

Inadequate sleep changes the brain, resulting in thinner gray matter, less neuroplasticity, poorer higher-level cognitive abilities (attention, working memory, inhibition, judgment, decision-making), lower motivation, and poorer academic functioning. None of these are losses teens can afford!

junpinzon/Thinkstock

Dr. Howard is assistant professor of pediatrics at Johns Hopkins University, Baltimore, and creator of CHADIS (www.CHADIS.com). She had no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline Medical News. E-mail her at pdnews@frontlinemedcom.com.

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

The Cardiovascular Insights for Primary Care Physicians eNewsletter Series summarizes key information and data on common cardiovascular issues facing primary care physicians today. 

Management of Acute Coronary Syndromes in Patients with Diabetes is the fifth eNewsletter in this series.

Click here to read the supplement. 

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

ATLANTA – Adding caplacizumab to standard therapy for acquired thrombotic thrombocytopenic purpura (aTTP) significantly improved platelet response and prevented recurrent episodes in an international, randomized, double-blind, phase 3 placebo-controlled trial.

“Patients were 55% more likely to achieve normalization of platelet count in the caplacizumab group, and this was highly significant,” Marie Scully, MD, said during a late-breaking presentation at the annual meeting of the American Society of Hematology.

Neil Osterweil/Frontline Medical News

SOURCE: Scully M et al., ASH 2017 Abstract LBA-1.

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

aotto@frontlinemedcom.com

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

aotto@frontlinemedcom.com

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP

SAN DIEGO – A history of head injury is associated with increased amyloid deposition in the brain, both globally and in the frontal cortex, according to PET imaging in 329 older adults without dementia.

Previous studies have found an association between head injury and later dementia, but the mechanism isn’t understood. The importance of the new investigation is that it “hints at pathophysiology. We were very excited” to find amyloid in the frontal cortex, “which is also associated with Alzheimer’s disease,” said lead investigator Andrea Schneider, MD, PhD, a neurology resident at Johns Hopkins University, Baltimore.

Increased amyloid deposition was not found in other areas associated with the disease, but frontal cortex involvement “does suggest perhaps a common” denominator, she noted.

M. Alexander Otto/Frontline Medical News

aotto@frontlinemedcom.com

SOURCE: Schneider A et al. ANA 2017 abstract M336WIP

Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

cnellist@frontlinemedcom.com

Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

cnellist@frontlinemedcom.com

Members of the Pediatric News Editorial Advisory Board share some of the events and findings of 2017 that they believe have or will have the most impact on pediatric practice.



Francis Rushton Jr., MD, practiced pediatrics in Beaufort, S.C. for 32 years, and currently is the medical director of S.C. Quality through Technology and Innovation in Pediatrics (QTIP), funded by the South Carolina Department of Health and Human Services.

Dropping the human papillomavirus (HPV) regimen to two shots from three shots, as recommended by the Centers for Disease Control and Prevention, appears to have really improved uptake of HPV immunization.

Preventive oral health in the pediatrician’s office is not really a new recommendation from 2017; we have been talking about fluoride varnish for over a decade. What is new is that we gradually are seeing fluoride varnish move into practice, up from 1,000 applications in pediatric offices in 2011 to close to 20,000 applications in South Carolina alone.

Pediatricians are being asked to screen more and more. We’re asked to do developmental screening, postpartum depression screening, autism screening, behavioral health screening, social determinants of health screening, parental concerns screening, etc. As a result, we now have multiple different screens with different schedules. The Survey of Well-Being of Young Children screening tool does it all – one screen at each preschool well visit from birth to age 5 years.

A different approach is to use CHADIS (Child Health and Development Interactive System), a for-profit venture where all the screens are loaded electronically.

Howard Smart, MD, is chairman of pediatrics at Sharp Rees-Stealy Medical Group, San Diego.

The switch to a two-dose schedule for HPV vaccination has improved both acceptance of the vaccine and the likelihood of timely completion of the HPV series.
 

Kelly Curran, MD, MA, is an assistant professor of pediatrics at the University of Oklahoma Health Sciences Center, Oklahoma City, practicing adolescent medicine.

The news from Australia is that the older meningitis B vaccine (MeNZB) provides some protection against Neisseria gonorrhoeae, as reported in the Lancet (2017 July 10. doi: 10.1016/S0140-6736[17]31449-6)! The newer version of the meningitis B vaccine Bexsero also contains the same outer membrane vesicle antigen. Given increasing bacterial resistance – and pan-resistant gonorrhea organisms already in some parts of the world – this is exciting news for the future!

The increased use of the reverse screening algorithm for syphilis is exciting. Although this has been “available” for several years, increasingly more physicians/laboratories are using this in practice. Our academic center – in a relatively high prevalence area for syphilis – recently switched to this screening method.



M. Susan Jay, MD, is a professor of pediatrics and section chief of adolescent medicine at the Medical College of Wisconsin and program director of adolescent health and medicine at the Children’s Hospital of Wisconsin, both in Milwaukee.

Suzanne C. Boulter, MD, is adjunct professor of pediatrics and community and family medicine at the Geisel School of Medicine at Dartmouth in Hanover, N.H.

I was very impressed with the recent American Academy of Pediatrics policy on human trafficking published in Pediatrics (2017 November. doi: 10.1542/peds.2017-3138), and think this is a new area of knowledge of which pediatricians need to be aware.

With all the news and social media about sexual misconduct by persons in power, I’m a bit concerned that there could be a fallout on pediatricians performing appropriate examinations on their patients that could be interpreted as something else.

Timothy J. Joos, MD, MPH, is a practicing clinician in combined internal medicine/pediatrics in Seattle. For the last decade, he has worked at a federally qualified community health center in Seattle serving a largely low-income and immigrant population.

With regard to practice-changing events for 2017, I don’t wish to downplay the numerous research advances over the year, but the advances cannot be made without funding, and they are not going to be practice-changing if they can’t reach the patients. We can’t ignore the uncertainty that the current political situation in 2017 has caused for our patients and their families, as well as for research and for the health care industry in general.

It is impossible to deny the important role government health care programs play in the health of our own patients and the health of the whole country. According to numbers from the Kaiser Family Foundation website, currently 38% of the estimated 74 million kids in this country are covered by Medicaid and CHIP programs. The numbers of uninsured children are at all-time lows at 5% (adults 10%). The current uncertainty of government funding is felt strongly by safety net providers such as community health centers that have traditionally seen the uninsured patients. The community health center where I work went from 35% of its patients being uninsured before the Affordable Care Act to about 15% now.

Efforts to dismantle the Affordable Care Act and reverse Medicaid expansions, as well as delays on funding to the CHIP program, have created uncertainty and anxiety across health care from the administrators and insurance companies to us – the providers – and the families we take care of. In addition, National Institutes of Health funding is threatened to be cut by 20%. 2017 will go down in history as the year of health care toxic stress (that is, unless 2018 is worse). As we celebrate the end of the year, we all deserve a Xanax and a Zantac.

cnellist@frontlinemedcom.com

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Clinical case

A 48-year-old man with cirrhosis and esophageal varices presents to the emergency department with hematochezia and hematemesis. Upon arrival to the floor, he has another bout of hematochezia and hematemesis. He appears pale. His pulse is 90 beats per minute, his blood pressure is 100/60 mmHg, and his respiratory rate is 14 breaths per minute. A complete blood count reveals a hemoglobin level of 7.8 g/dL and hematocrit of 23.5%. Should he receive a blood transfusion?

Introduction

Anemia is one of the most frequent conditions in hospitalized patients. Anemia is variably associated with morbidity and mortality depending on chronicity, etiology, and associated comorbidities. Before the 1980s, standard practice was to transfuse all patients to a hemoglobin level greater than 10 g/dL and/or a hematocrit greater than 30%. However, with concerns about the potential adverse effects and cost of transfusions, the safety and effectiveness of liberal versus restrictive transfusion thresholds became the subject of many studies.

Tomasz Gierygowski/Thinkstock

Overview of the data

Critically ill patients

The Transfusion Requirements in Critical Care (TRICC) trial, published in 1999, was the first large clinical trial examining the safety of restrictive transfusion thresholds in critically ill patients.³

Acute upper GI bleed

Acute upper gastrointestinal bleeding (UGIB) is one of the most common indications for RBC transfusion.

Perioperative patients

Transfusion thresholds have been studied in large randomized trials for perioperative patients undergoing cardiac and orthopedic surgery.

The Transfusion Requirements after Cardiac Surgery (TRACS) trial, published in 2010, randomized patients undergoing cardiac surgery at a single center to a liberal strategy of blood transfusion (to maintain a hematocrit 30% or greater) or a restrictive strategy (hematocrit 24% or greater).⁷ Mortality and severe morbidity rates were noninferior in the restrictive strategy group. Mean hemoglobin concentrations were 10.5 g/dL in the liberal-strategy group and 9.1 g/dL in the restrictive-strategy group. Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications and death at 30 days.

Acute coronary syndrome, stable coronary artery disease, and congestive heart failure

Anemia is an independent predictor of major adverse cardiovascular events in patients with acute coronary syndrome.⁹ However, it remains controversial if transfusion has benefit or causes harm in patients with acute coronary syndrome. No randomized controlled trials have yet been published on this topic, and observational studies and subgroups from randomized controlled trials have yielded mixed results.

Similarly, there are no randomized controlled trials examining liberal versus restrictive transfusion goals for asymptomatic hospitalized patients with stable coronary artery disease (CAD). However, patients with CAD were included in the TRICC and FOCUS trials.^3,8 Of patients enrolled in the TRICC trial, 26% had a primary or secondary diagnosis of cardiac disease; subgroup analysis found no significant differences in 30-day mortality between treatment groups, similar to that of the entire study population.³ In a subgroup analysis of patients with “cardiovascular disease” the FOCUS trial found no difference in outcomes between a restrictive and liberal transfusion strategy, although there was a marginally higher incidence of myocardial infarction in the restrictive arm in the entire study population.⁸

Although some studies have included patients with congestive heart failure (CHF) as a subgroup, these subgroups are often not powered to show clinically meaningful differences. The risk of volume overload is one explanation for why transfusions may be harmful for patients with CHF.

Based on these limited available data, the AABB guidelines recommend a “restrictive RBC transfusion threshold (hemoglobin level of 8 g/dL)” for patients “with preexisting cardiovascular disease,” without distinguishing among patients with acute coronary syndrome, stable CAD, and CHF, but adds that the “threshold of 7 g/dL is likely comparable with 8 g/dL, but randomized controlled trial evidence is not available for all patient categories.”¹

Of note, certain patient populations, such as those with end-stage renal disease, oncology patients (especially those undergoing active chemotherapy), and those with comorbid conditions such as thrombocytopenia and coagulopathy are specifically excluded from the AABB guidelines. The reader is referred to guidelines from respective specialty societies for further guidance.
 

Back to our case

This 48-year-old man with cirrhosis and esophageal varices presenting with ongoing blood loss due to hematochezia and hematemesis with a hemoglobin of 7.8 g/dL should be transfused due to his active bleeding; his hemoglobin level should not be a determining factor under such circumstances. This distinction is one of the most fundamental in interpreting the guidelines, that is, patients with hemodynamic insult, symptoms, and/or ongoing bleeding should be evaluated clinically, independent of their hemoglobin level.

Bottom line

Although recent guidelines generally favor a more restrictive hemoglobin goal threshold, in the presence of active blood loss or hemodynamic instability, blood transfusion should be considered independent of the initial hemoglobin level.

Key Points

• The AABB guidelines recommend transfusing stable general medical inpatients to a hemoglobin level of 7 g/dL.
• For patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease, a transfusion threshold of 8 g/dL is recommended.
• Patients with hemodynamic instability or active blood loss should be transfused based on clinical criteria, and not absolute hemoglobin levels.
• Patients with acute coronary syndrome, severe thrombocytopenia, and chronic transfusion–dependent anemia are excluded from these recommendations.
• Further studies are needed to further refine these recommendations to specific patient populations in maximizing the benefits and minimizing the risks of blood transfusions.

Quiz

In which of the following scenarios is RBC transfusion LEAST indicated?

• A. Active diverticular bleed, heart rate 125 beats/minute, blood pressure 85/65 mm HG, hemoglobin 10.5 g/dL
• B. Septic shock in the ICU, hemoglobin 6.7 g/dL
• C. Pulmonary embolism in the setting of stable coronary artery disease and hemoglobin 8.7 g/dL
• D. Lymphoma on chemotherapy, hemoglobin 7.5 g/d, patient becomes dizzy when standing

Answer: C – A hemoglobin transfusion goal of 8.0 g/dL is recommended for patients with cardiovascular disease. The patient in answer choice A has active blood loss, tachycardia, and hypotension, all pointing to the need for blood transfusion irrespective of an initial hemoglobin level greater than 8.0 g/dL. The patient in answer choice B has a hemoglobin level less than 7.0 g/dL, and the patient in choice D is symptomatic, possibly from anemia, as well as on chemotherapy, therefore making transfusion a reasonable option.

Dr. Sampat, Dr. Berger, and Dr. Manian are hospitalists at Massachusetts General Hospital, Boston.

References

1. Carson JL et al. Clinical Practice Guidelines From the AABB: Red Blood Cell Transfusion Thresholds and Storage. JAMA. 2016;316:2025-35.

2. Dwyre DM et al. Hepatitis B, hepatitis C and HIV transfusion-transmitted infections in the 21st century. Vox Sang. 2011;100:92-8.

3. Hébert PC et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med. 1999;340:409-17.

4. Holst LB et al. Lower versus higher hemoglobin threshold for transfusion in septic shock. N Engl J Med. 2014;371:1381-91.

5. Villanueva C et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med. 2013;368:11-21.

6. Jairath V et al. Restrictive versus liberal blood transfusion for acute upper gastrointestinal bleeding (TRIGGER): a pragmatic, open-label, cluster randomised feasibility trial. Lancet. 2015;386:137-44.

7. Hajjar LA et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010;304:1559-67.

8. Carson JL et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011;365:2453-62.

9. Sabatine MS et al. Association of hemoglobin levels with clinical outcomes in acute coronary syndromes. Circulation. 2005;111:2042-9.

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

Every prevention effort or treatment has its own risks. Gynecologists must consider the risk for blood clots from using estrogen-containing oral contraceptives versus the risk of blood clots from pregnancy. Endocrinologists must weigh the risk of decreased bone mineral density versus premature closure of growth plates when starting pubertal blockers for children suffering from precocious puberty. Psychologists and primary care providers must consider the risk for increased suicidal thoughts while on selective serotonin reuptake inhibitors versus the risk of completed suicide if the depression remains untreated.

LemonTreeImages/Thinkstock

NIAID

Dr. Montano is an assistant professor of pediatrics at the University of Pittsburgh and an adolescent medicine physician at Children’s Hospital of Pittsburgh of UPMC. Email him at pdnews@frontlinemedcom.com.

Resource

CDC website on PrEP: https://www.cdc.gov/hiv/risk/prep/index.html, with provider guidelines.
 

References

1. Centers for Disease Control and Prevention. HIV Among Youth fact sheet, April 2017.

2. Centers for Disease Control and Prevention. HIV Surveillance Report, 2015; vol. 27.

3. Centers for Disease Control and Prevention. HIV Among Transgender People.

4. Kaiser Family Foundation. National survey of teens and young adults on HIV/AIDS, Nov. 1, 2012. .

5. J Acquir Immune Defic Syndr. 2016;73(5):547-55.

6. Serving our youth: Findings from a national survey of services providers working with lesbian, gay, bisexual and transgender youth who are homeless or at risk of becoming homeless (The Williams Institute with True Colors and The Palette Fund, 2012).

7. Injustice at every turn: A report of the national transgender discrimination survey (National Center for Transgender Equality and National Gay and Lesbian Task Force, 2011).

8. J Acquir Immune Defic Syndr. 2010 Apr;53(5):661-4.

9. Centers for Disease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States: A clinical practice guideline, 2014.

10. JAMA Pediatr. 2017;171(11):1063-71.

11. J Int AIDS Soc. 2016;19. doi: 10.7448/IAS.19.7.21107.
 

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.

The Diagnosis: Congenital Unilateral Nevoid Telangiectasia

Two weeks later the patches were noticeably lighter (Figures 1A and 1B). She continued to be in good health, but gynecomastia was notably present on examination (Figure 1C). At 3 months of age, all patches on the right arm, superior aspect of the chest, and superior aspect of the back had resolved, along with the gynecomastia (Figure 2).

This case describes the rare condition of congenital unilateral nevoid telangiectasia (UNT). Unilateral nevoid telangiectasia is a rare cutaneous vascular condition first described by Blaschko¹ in 1899. It is characterized by the presence of unilateral superficial telangiectases occurring most often in the cervical and upper thoracic dermatomes in a linear pattern.² Females are more often affected than males (2:1 ratio), and cases of UNT are either congenital or acquired.³ Although most UNT cases are acquired and often found in females, approximately 15% of cases are congenital and are comprised largely by males. Acquired cases have been hypothesized to occur in association with hyperestrogenemic states such as pregnancy, puberty, oral contraceptive use and hormonal therapy, alcoholism, and liver disease including hepatitis B and C infections.^4,5 There is conflicting evidence as to whether there is an absolute increase in the presence of estrogen and progesterone receptors in the skin, as many case reports show no increase. Instead, others hypothesize that the condition is actually a result of somatic mosaicism and that the cutaneous lesions are genetically predisposed to becoming visibly evident under conditions of elevated estrogen.²

In our case, we hypothesize that the cause was elevated maternal estrogen levels present at higher than normal levels in the fetal circulation. The presence of gynecomastia seen in our patient supports the hypothesis that increased circulating estrogen may be present in infants with UNT.